The present invention relates to a method of mass spectrometry and a mass spectrometer that filters product ions.
Approaches such as MSe and HDMSe have proven useful in unbiased high sensitivity MSMS applications. In MSe the ion population is repeatedly switched between two or more modes of operation. In one of these modes of operation the ion population remains substantially un-fragmented and thus predominately consists of precursor ions. In another one of these modes, the ion population undergoes fragmentation and thus the resulting population predominately consists of product ions. The two or more populations are acquired using a mass spectrometer and product ions are assigned to precursor ions based on chromatographic precursor peak profile characteristics such as liquid chromatography retention time or peak shape. Whilst this approach has proven useful it does suffer from limited precursor ion to product ion assignment specificity in complex mixtures due to the relatively low peak capacity or resolution of the liquid chromatographic separation.
An improvement to this approach introduces a fast ion mobility separation device between the liquid chromatography separation stage and the fragmentation stage. This technique is commonly known as HDMSe. Whilst the peak capacity of each of ion mobility separation (IMS) and liquid chromatography separation is relatively low, the two separation techniques are not strongly correlated and so the combination of the techniques results in a substantially increased peak capacity at the point of fragmentation. In HDMSe the fidelity of the ion mobility separation is maintained through the fragmentation process and through subsequent devices, allowing precursor ions to be assigned to fragment ions based on IMS drift times and peak shapes as well as liquid chromatography retention times and peak shapes. The combination of these two approaches greatly increases the precursor ion to product ion assignment specificity in complex mixtures.
Data directed analysis (DDA) has conventionally been seen as an alternative approach to MSe and HDMSe. In DDA techniques, a MS survey scan is used to identify components of interest and once these components have been identified they are isolated using a mass filter, for example a quadrupole mass filter, before undergoing fragmentation and fragment ion mass analysis. The information in the fragment ion mass spectra, together with the precursor ion information, leads to a highly specific/selective experiment. In some application areas MSe and DDA have been combined to produce a more targeted DDA experiment that is sometimes referred to as ‘MSe triggered DDA’. For example, product and precursor ion populations may be interrogated for potential neutral losses by looking for differences in mass to charge ratio values, that are associated with a target neutral loss, between peaks in the precursor and product ion spectra. This may be useful as a neutral loss can be indicative of a particular group of components of interest. Once a potential neutral loss has been identified the quadrupole mass filter may isolate the precursor ion, which is then fragmented and the fragment ions mass analysed. As with MSe techniques, this method suffers from relatively low specificity in complex mixtures.
It is therefore desirable to provide an improved method of mass spectrometry and an improved mass spectrometer.